The objective of the proposed experiments is to determine the effects of morphine treatment on the progression of a live bacterial infection in naive and immunized animals, and begin to understand the role of nitric oxide in that process. To achieve these goals, the proposed research uses a subcutaneous chamber model, whereby a stainless steel coil implanted subcutaneously in the rat serves as the site of injection of Porphyromonas gingivalis strain A7436 bacteria. In all studies, animals receive saline or morphine prior to introduction of live bacteria into the chamber. These studies investigate bacterial dissemination from the chamber to the blood, spleen, liver, and lung. The level of nitric oxide production will be determined by measuring the levels of inducible nitric oxide synthase mRNA and protein levels in the spleen, lung, and liver. Plasma nitrite/nitrate concentrations also will be determined. Specific Aim I determines the dose-dependent effect of morphine treatment on dissemination of P. gingivalis strain A7436 to blood and tissues and nitric oxide activity in naive animals. Specific Aim II determines the pharmacological specificity of morphine on bacterial dissemination and nitric oxide activity by assessing the effect of the opiate antagonist, naltrexone, administered prior to morphine treatment. Specific Aim III determines the effect of morphine on bacterial dissemination and nitric oxide activity in animals previously immunized with heat killed A7436 bacteria. The results of these studies will expand the known effects of morphine on immune function and provide a greater understanding of the effects of morphine on infection. The conduct of these experiments will afford the applicant with the opportunity to acquire research experience in the application of molecular and microbiological techniques to the study of the pharmacological effects of opioids on immune function and the study of infection.